Utilizing Regulatory T Cells in the Treatment and Prevention of Diabetes Mellitus Type I
Alexander Sanders
Introduction. Type I Diabetes Mellitus is a multifactorial autoimmune disease that targets and destroys pancreatic islet cells which produce insulin. It is most often diagnoses during childhood and affects millions of people around the world. While much is known about the disease and how to treat it, significant research is still needed on the underlying mechanisms of diabetes mellitus–specifically with regard to the role that regulatory T cells play in allowing the disease to occur. The disease develops after evading multiple layers of the immune system’s checks and balances. First, autoreactive T cells are generated due to a variety of mutate genes ranging from HLA’s to MHC complex molecules. Subsequently, a reduction in levels of Foxp3 regulatory T cells and TGF-β enable the autoreactive cell to activate and destroy the pancreatic insulin-producing cells. Numerous in vitro and animal studies have recently shown that reactivation of the regulatory T cell system can dramatically reduce the aggressiveness of diabetes mellitus and can potentially restore function of surviving insulin-producing cells. Methods. In this review, we will analyze two particular studies that looked at regulatory T cell activation, one in NOD mice and the other in diabetic patients. These studies were chosen based on their recency, their thorough data collection, and their citation in numerous other journals. Results. These studies show that proper reactivation of the regulatory T cell system can reduce the number of autoimmune T cells and can increase the number of regulatory T cells. Furthermore, the reactivation can potentially be sustained with memory T cells and can lead to increases in insulin production from the surviving pancreatic islets. This basic science research is currently being applied to clinical medicine and early results show promise in helping to reduce the detriment that type I diabetes mellitus has on patients. There are many promising candidates that have demonstrated early success in animal studies in vaccination. Current efforts are focusing on improving the insulin mimetope used to elicit a stronger immune response and in refining the dosing and scheduling pattern. Conclusion. While the results have been positive, there are still questions surrounding the clinical application of such a vaccine on improving current treatment methods. Future studies are needed to further identify the genetic and environmental predictors of Type I DM as well as the viability of a vaccine in generating long term immunity.
- Bonner SM, Pietropaolo SL, Fan Y, et al. Sequence Variation in Promoter of Ica1 Gene, Which Encodes Protein Implicated in Type 1 Diabetes, Causes Transcription Factor Autoimmune Regulator (AIRE) to Increase Its Binding and Down-regulate Expression. The Journal of Biological Chemistry. 2012;287(21):17882-17893. doi:10.1074/jbc.M111.319020.
- Chruscinski A, Sadozai H, Rojas-Luengas V, et al. Role of Regulatory T Cells (Treg) and the Treg Effector Molecule Fibrinogen-like Protein 2 in Alloimmunity and Autoimmunity. Rambam Maimonides Medical Journal. 2015;6(3):e0024. doi:10.5041/RMMJ.10209.
- Qiao, Yong-Chao, Jian Shen, and Xue-Zhi Hong. “Changes of Regulatory T Cells, Transforming Growth Factor-beta and Interleukin-10 in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis.” Clinical Immunology 170 (2016): 61-69. Sept. 2016. Web.
- Serr, Isabelle, Rainer W. Furst, Peter Achenbach, Martin G. Scherm, Fusun Gokmen, Florian Haupt, Eva-Maria Sedlmeier, Annette Knopff, Leonard Shultz, Richard A. Willis, Anette-Gabriele Ziegler, and Carolin Daniel. “Type 1 Diabetes Vaccine Candidates Promote Human Foxp3 Treg Induction in Humanized Mice.” Nature Communications 7 (2016): 10991. Web.
- Zhang J, Gao W, Yang X, et al. Tolerogenic Vaccination Reduced Effector Memory CD4 T Cells and Induced Effector Memory Treg Cells for Type I Diabetes Treatment. Piccirillo CA, ed. PLoS ONE. 2013;8(7):e70056. doi:10.1371/journal.pone.0070056.
- Zhang, L., F. Crawford, L. Yu, A. Michels, M. Nakayama, H. W. Davidson, J. W. Kappler, and G. S. Eisenbarth. “Monoclonal Antibody Blocking the Recognition of an Insulin Peptide-MHC Complex Modulates Type 1 Diabetes.” Proceedings of the National Academy of Sciences 111.7 (2014): 2656-661. NCBI. Web.